Laboratory central control unit method and system

ABSTRACT

The present disclosure provides a method for coordinating data between a plurality of sample processing systems comprising: providing, using a central control unit, data to a pre-analytical sample processing system identifying a sample undergoing pre-analytical processing, receiving data, at the central control unit, indicating the transfer of the sample to an analytical system, providing, from the central control unit (CCU), data associated with the sample to the analytical system, and receiving a result associated with the sample from the analytical system.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is related to and claims the benefit of U.S.Provisional Patent Application No. 61/262,497 filed Nov. 18, 2009,entitled “Laboratory Central Control Unit Method And System”, herebyincorporated by reference in its entirety.

BACKGROUND 1. Field of the Art

The present disclosure relates to control of and coordination betweenautomated sample processing systems, and provides systems and methodsthat permit the coordination of data flow between high-throughputspecimen processing systems. Systems according to embodiments may tracksamples being processed in a plurality of systems including, but notlimited to, pre-analytical systems, analytical systems, and LaboratoryInformation Systems (LISs). The coordination of data between a pluralityof systems may provide tracking of samples across a plurality of systemsand may provide remote monitoring of a plurality of instruments,samples, and testing materials. Aspects of the disclosed systems may beused independently or in other systems. In exemplary embodiments thesecentral control units (CCU's) are used in conjunction with and tocontrol parameters in automated high throughput systems for detectingproteins or nucleic acids or pathogens in clinical samples, especiallyviruses and bacteria such as HPV and Chlamydia. In some embodimentsthese CCU's may regulate high throughput systems that include nucleicacid amplification reactions.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a system for control of and coordination betweenautomated sample processing systems, according to one embodiment.

FIG. 2 shows a module for control of and coordination between automatedsample processing systems, according to one embodiment.

FIG. 3 depicts a method for control of and coordination betweenautomated sample processing systems, according to one embodiment.

FIG. 4 depicts a system for acceptance of and control of manuallycreated samples and automated analysis of such samples, according to anembodiment.

FIG. 5. is a diagram of exemplary inputs and outputs of a CCU, accordingto an embodiment.

FIG. 6 is a diagram illustrating components of a CCU operator interface,according to an embodiment.

FIG. 7 is an exemplary graphical view of the logical composition of themajor components of a CCU system, according to an embodiment.

FIG. 8 is a diagram depicting components of a file watcher service,according to an embodiment.

FIG. 9 is a diagram illustrating module dependencies and interactions,according to an embodiment.

FIG. 10 depicts a diagram of a physical view of the CCU software interms of the major software subcomponents of CCU, according to anembodiment.

FIG. 11 shows a more detailed view of the MVVM design patternimplemented in the CCU Operator Interface, according to an embodiment.

FIG. 12 is a sequence diagram illustrating communication between anInstrument Client Library and an Instrument Service, according to anembodiment.

FIG. 13 is a diagram relating logical components of an AS, a CCU, and aPAS, to the physical component names, according to an embodiment.

FIG. 14 depicts an exemplary organizational chart of interface screens,according to an embodiment.

FIG. 15 depicts a user interface for viewing a sample worklist,according to an embodiment.

FIG. 16 depicts a user interface for viewing a sample location report,according to an embodiment.

FIG. 17 depicts a user interface for viewing preparation and testingtimelines for Analytical and Pre-Analytical systems, according to anembodiment.

FIG. 18 depicts a user interface for remote monitoring of apre-analytical system, according to an embodiment.

FIG. 19 depicts a user interface for releasing samples from a worklistfor genotyping, according to an embodiment.

FIG. 20 depicts a user interface for reflex sample informationverification, according to an embodiment.

FIG. 21 depicts a user interface for selecting a view of reflexinformation according to an embodiment.

FIG. 22 depicts a user interface for a plate map highlighting samplesselected for reflex testing, according to an embodiment.

FIG. 23 depicts a user interface for sample reflex listing, according toan embodiment.

FIG. 24 depicts a user interface for sample location reporting forreflex samples, according to an embodiment.

FIG. 25 depicts a user interface for selecting reports, according to anembodiment.

FIG. 26 depicts a user interface for alerts associated with attachedinstruments, according to an embodiment.

FIG. 27 depicts a user interface displaying an alert detail, accordingto an embodiment.

FIG. 28 depicts a user interface for viewing instrument statusinformation, according to an embodiment.

FIG. 29 depicts a user interface for providing operator help, accordingto an embodiment.

FIG. 30 depicts a method for analyzing a plate processed on anAnalytical System, according to an embodiment.

FIG. 31 depicts a method for analyzing a calibrator replicate, accordingto an embodiment.

FIG. 32 depicts a method for assay control evaluation, according to anembodiment.

DETAILED DESCRIPTION

The present disclosure provides various exemplary embodiments of systemsfor control of and coordination between automated sample processingsystems, Laboratory Information Systems (“LISs”), and other systems, aswell as methods that permit the coordination of data flow betweenhigh-throughput specimen processing systems. Systems according toembodiments may use a Central Control Unit (“CCU”) to track samplesbeing processed in a plurality of systems including, but not limited to,pre-analytical systems, analytical systems, and Laboratory InformationSystems (“LISs”). The coordination of data between a plurality ofsystems may provide data communication and testing coordination acrosssystems and may provide remote monitoring of a plurality of instruments,samples, and testing materials. Exemplary pre-analytical and analyticalsystems and assay methods that can be used for detection of HPV, CT/GC,cancer markers, or other constituents of clinical samples are describedin: U.S. patent application Ser. No. 12/062,950, filed Apr. 4, 2008;U.S. Provisional Patent Application Ser. No. 60/910,565 filed Apr. 6,2007; U.S. Provisional Patent Application Ser. No. 61/113,855, filedNov. 12, 2008; U.S. Provisional Patent Application Ser. No. 61/122,621,filed Dec. 15, 2008; U.S. Provisional Patent Application Ser. No.61/185,081, filed Jun. 8, 2009, entitled “Automated Human PapillomavirusAssay and System”; U.S. Provisional Patent Application Ser. No.61/242,671, filed Sep. 15, 2009; U.S. patent application Ser. No.12/855,306, filed Oct. 9, 2009, entitled “OPEN PLATFORM AUTOMATED SAMPLEPROCESSING SYSTEM”; U.S. patent application Ser. No. 12/855,304, filedOct. 9, 2009, entitled “AUTOMATED ASSAY AND SYSTEM”; U.S. ProvisionalApplication Ser. No. 61/045,952, filed Apr. 17, 2008, entitled“COMPOSITIONS, METHODS, AND KITS FOR DETERMINING NUCLEIC ACID”; U.S.Provisional Application Ser. No. 61/113,841, filed Nov. 12, 2008,entitled “COMPOSITIONS, METHODS, AND KITS FOR DETERMINING NUCLEICACID,”; U.S. Provisional Application Ser. Nos. 61/231,371, filed Aug. 5,2009, entitled “METHODS AND KITS FOR ISOLATING NUCLEIC ACIDS USING ANANION EXCHANGE MATRIX”; U.S. Provisional Application Ser. No.61/147,862, filed Jan. 28, 2009, entitled “SEQUENCE SPECIFIC LARGEVOLUME SAMPLE PREP SOLUTION UTILIZING HYBRID CAPTURE TECHNOLOGY,”;61/147,623, filed Jan. 27, 2009, entitled “ISOTHERMAL HELICASE DEPENDENTMULTIPLEX ASSAY FOR DETECTION OF CHLAMYDIA TRACHOMATIS AND NEISSERIAGONORRHOEAE WITH FLUORESCENCE ENDPOINT DETECTION,”; U.S. Ser. No.12/426,076, filed Apr. 17, 2009; U.S. Provisional Application Ser. No.61/108,687, filed Oct. 27, 2008, entitled “NOVEL FAST RESULTS HYBRIDCAPTURE ASSAY”; 61/179,848, filed May 1, 2009, entitled “NOVEL FASTRESULTS HYBRID CAPTURE ASSAY”; U.S. patent application Ser. No.12/605,540, filed Oct. 26, 2009, entitled “Fast Results Hybrid CaptureAssay and System”; Ser. No. 12/605,605, filed Oct. 26, 2009, entitled“Fast Results Hybrid Capture Assay On An Automated Platform”; U.S. Pat.No. 6,228,578, U.S. Provisional Application No. 61/180,821, U.S.Provisional Application No. 61/147,623; Tong et al., “Development ofisothermal TaqMan assays for detection of biothreat organisms,”BioTechniques Vol. 45, 543-557 (2008); Motré et al. “Enhancinghelicase-dependent amplification by fusing the helicase with the DNApolymerase,” Gene Vol. 420, 17-22 (2008); Chow et al., “Application ofIsothermal Helicase-Dependent Amplification with a disposable DetectionDevice in a Simple Sensitive Stool Test for Toxigenic Clostridiumdifficile,” J. Mol. Diagnostics Vol. 10 (5), 452-458 (2008); Li et al.,“Primase-based whole genome amplification,” Nucleic Acids Research36(13): e79 (2008); Goldmeyer et al., “Identification of Staphylococcusaureus and Determination of Methicillin Resistance Directly fromPositive Blood Cultures by Isothermal Amplification and DisposableDetection Device,” J. Clin. Microbiol Vol. 46, 1534-1536 (2008); Kong etal., “New isothermal molecular diagnostic platforms,” IVD TechnologyNovember issue (2007); Goldmeyer et al., “Development of a novelone-tube isothermal RT-tHDA platform for rapid RNA detection,” J. Mol.Diagnostics Vol. 9, 639-644. (2007); Xu et al., “Simultaneousamplification and screening of whole plasmids using the T7 bacteriophagereplisome,” NAR 34(13): e98 (2006); An et al., “Characterization of aThermostable UvrD Helicase and its Participation in Helicase DependentAmplification,” The Journal of Biological Chemistry Vol. 280,28952-28958 (2005); and Vincent et al., “Helicase Dependent IsothermalDNA Amplification,” EMBO reports Vol. 5, 795-800 (2004), the contents ofeach of which is incorporated by reference herein.

The systems described herein can be used to monitor and manage systemsperforming steps required in many common clinical or research laboratorymethods. Exemplary embodiments monitor systems which can be used with aDNA analysis assay, such as the Digene HPV eHC test by QIAGENGaithersburg, Inc, in Gaithersburg, Md. (“Qiagen”). Other monitoredsystems may utilize the Next Generation Hybrid Capture® High Risk assaydeveloped by QIAGEN Gaithersburg, Inc, in Gaithersburg, Md. (“Qiagen”).This assay may maintains high clinical sensitivity for high gradecervical disease established by the Hybrid Capture 2 during numerouslarge scale clinical studies, while creating a highly specific result.Examples of this and other assays that can be coordinated by embodimentsof the systems described herein are disclosed in U.S. application Ser.No. 12/588,306, filed Oct. 9, 2009, entitled “OPEN PLATFORM AUTOMATEDSAMPLE PROCESSING SYSTEM”; U.S. application Ser. No. 12/605,540, filedOct. 26, 2009, entitled “FAST RESULTS HYBRID CAPTURE ASSAY AND SYSTEM”;“U.S. application Ser. No. 12/605,605, filed Oct. 26, 2009, entitled“FAST RESULTS HYBRID CAPTURE ASSAY ON AN AUTOMATED PLATFORM”; and U.S.Provisional Applications 61/108,687 filed Oct. 27, 2008; U.S.Provisional Application 61/174,848 filed on May 1, 2009; the contents ofall of which are incorporated herein by reference in their entireties.

It will be understood that the foregoing assays are exemplary and thatthe present system may be used for managing and coordinating databetween systems performing other clinical processes or detecting othermoieties such as other nucleic acids, proteins, small molecules, cells,viruses, bacteria, fungi, yeast, mycoplasma and the like. Embodimentsdescribed herein may be adapted to provide the ability to manage andcoordinate between systems performing a diverse set of common laboratoryoperations in a standard tube or plate format, with different systemsreadily constructed from combinations of processing stations to performsteps required in virtually any protocol. In some embodiments the CCUmay be used to control parameters of automated systems that allow forthe detection of analytes which may be comprised in plates and/or tubesthereby providing for greater flexibility.

The CCU may connect and interface instruments (pre-analytical,analytical) and transfer load lists between the devices. The CCU mayfacilitate a high through-put automated diagnostic platform designed inthe format of a laboratory system. It may serve as the data portal andmediator of data flow in this configuration and may have the capacity toconnect the system to the LIS. The CCU may support tracking and trendingof controls, perform result interpretation using raw data originatingfrom the analytical instrument and report and print results generated bythe analytical instrument.

According to some embodiments, the CCU may accept Manual Pre-analyticalChemistry (MPAC) input from a user. The CCU may provide a user interfacefor accepting user created plate maps and other data associated withmanually created samples. As described in greater detail in reference toFIG. 4 below, the CCU may receive input via barcode readers and otherinterfaces. The CCU may allow manually created samples to then betransferred to an analytical system for processing.

The CCU may serve as a central hub of a high through-put automateddiagnostic platform. According to some embodiments, the CCU may beresponsible for the following: primary data repository for a highthrough-put automated diagnostic platform; remote monitoring of a highthrough-put automated diagnostic platform system status; management ofdataflow between the instruments in a high through-put automateddiagnostic platform; maintaining traceability for one or more samples,reagents, and other materials used on the system; maintaining adequateinventory control of samples, reagents and other materials used on thesystem, performance of data reduction to determine reportable resultsfor one or more specimens run on the system; releasing results (e.g., toprinted reports or to an LIS); and test order management for reflextesting to a genotype test.

Referring now to FIG. 1, an exemplary embodiment of a Central ControlUnit is described in detail. FIG. 1 depicts a system for control of andcoordination between automated sample processing systems, according toan embodiment. Central control unit (“CCU”) 102 may be a PC containingcontroller software which may be communicatively coupled to a pluralityof processing systems such as, for example, pre-analytic system (“PAS”)104 and analytical system (“AS”) 106. CCU 102 may also becommunicatively coupled to other systems such as Laboratory informationsystem 108 and wireless communication device 110.

The PAS 104 or other embodiments of a pre-analytic system may be used inconjunction with an analytical system that analyzes or tests the samples(such as by analyzing DNA that may be present in the sample). Forexample, analytical system 106 may be an analytical system may becapable of carrying out the steps of a nucleic acid detection assay suchas those described in Qiagen's Hybrid Capture 2 assay or QIAensembleassay protocols. Such steps may include sample loading, target nucleicacid denaturation, probe hybridization, target capture, signalproduction, signal detection and assay result reporting. An exemplaryanalytical system that may be used to perform these or other assays isthe QIAensemble 2000, available from Qiagen.

The exemplary PAS 104 may be a generally self-contained unit havingvarious input and output locations at which an operator can providesupplies and remove waste and processed samples. In the exemplaryembodiment, the PAS 104 may include a sample rack input, a sample rackoutput, a control vial and reject vial access point, a first pipette tipinput, an ETU input, reagent trays, a second pipette tip input, a sampleplate input, a sample plate output, and one or more solid waste outputs.PAS 104 may be adapted to process biological samples, includingliquid-cased cytology (LBC) samples into standard 96-well platescontaining the extracted sample nucleic acid. During processing, thesamples may be taken from standard sample containers, and processed in astrip of test tubes, called the extraction tube unit (“ETU”). Accordingto some embodiments, 384 well plates may be used.

Central control unit (CCU) 102 may be used to control and/or monitor thePAS 104 and/or a downstream analytical system, and an exemplary CCU mayprovide a processing interface between the PAS and the analyticalsystem. For example, a CCU may be combined with a PAS and an analyticalsystem to perform all of the steps necessary to pre-process and test asample according to the Hybrid Capture 2 or QIAEnsemble assay protocols.

The CCU and other interfaced systems (e.g., PAS 104 and AS 106) maydesigned to be used in a high volume laboratory. The CCU may be designedfor use in a laboratory environment where exposure to chemical spillsand other contaminations is possible. According to some embodiments, theCCU and other interfaced systems (e.g., PAS 104 and AS 106) may designedto be used by trained laboratory technicians. Help files may be providedon the CCU to provide on-screen support in order to resolve questionsthat a trained operator might have. In addition, approved labeling mayalso be provided to answer questions that may arise during use of theCCU and/or interfaced systems. Although illustrated as connected to asingle PAS and a single AS, according to some embodiments CCU 102 maysupport a plurality of PAS and a plurality of AS (e.g., four PAS andfour AS systems). According to some embodiments, CCU 102 may acceptmanually created samples and may allow transfer of manually createdplates to an AS for processing.

CCU 102 may be a desktop computer, a laptop computer, a server, or othercomputer. According to some embodiments, CCU 102 may have a number offeatures facilitating use in a laboratory environment. CCU 102 may havea touch screen that may be used by an operator wearing gloves. CCU 102may have a sealed keyboard that may be used in a laboratory environmentby an operator wearing gloves. CCU 102 may be capable of running one ormore operating systems (e.g., Microsoft Windows Vista for EmbeddedSystems, Microsoft Windows Vista, Mac OS X, Linux, etc.). Exemplaryspecifications of CCU 102 may include:

-   -   a processor speed of 3 GHz;    -   4 GB of system memory;    -   at least one 80 GB hard drive;    -   at least one USB (“Universal Serial Bus”) 2.0 or USB (“Universal        Serial Bus”) 3.0 Standard-A port;    -   one or more components for producing audio output (e.g.,        internal speakers, external speakers, and a soundcard or        integrated audio circuitry);    -   at least one optical media drive capable of reading and writing        CD-R, CD-RW, DVD-R, DVD-RW, DVD+R and DVD+RW disks;    -   one or more network interfaces (e.g., a 100Base-T, 1000Base-T        Ethernet interface); and    -   advanced graphics capabilities (e.g., support for running        DirectX 9 graphics with: a WDDM (“Windows Display Driver Model”)        Driver, 128 MB graphics memory, a Pixel Shader 2.0 supported in        hardware, and support for 32 bits per pixel).

CCU 102 may also be equipped with one or more external devices such as,for example, a hand-held barcode reader, a keyboard (e.g., United StatesQWERTY keyboard or a US-International QWERTY keyboard); a display (e.g.,a 17″ touch screen monitor that supports a resolution of 1280×1024pixels.)

CCU 102 may be communicatively coupled to a network (e.g., an isolated100Base-T or 1000BaseT Ethernet network dedicated to the CCU andinterfaced systems) which may be used to connect CCU 102 to PAS 104 andAS 106 via network connections 116 and 118 respectively. According tosome embodiments, this network may use TCP/IP. Additional systems orcomponents may be connected to this network, including, but not limitedto, additional PASs, additional analytical systems, and one or moreprinters. CCU 102 may have access to the printer which may be capable ofprinting reports, logs, and other documents originating from the CCU, ananalytical instrument, and a pre-analytical instrument. Exemplarycomponents of the network may include Ethernet hubs, Ethernet switches,one or more uninterruptible power supplies (UPS) (e.g., one or more UPSsufficient to power the network infrastructure for 15 minutes).According to some embodiments, only the Pre-Analytical Systems (PASs),Analytical Systems (AS), and the CCU may be connected to the network.Furthermore, the network may be the only data communication interfacewith the Pre-Analytical Systems (PASs) and the Analytical Systems (AS).

According to some embodiments, CCU communication with a PAS may includebi-directional communication for a range of activities including, butnot limited to: startup, setup, processing, on-going communication, anddata updates. For example, startup data may include registration of aninstrument (e.g., a PAS), receipt of data (e.g., item container data,reagent container data, sample container data, well information, etc.).The CCU may also receive a test schedule from one or more Pre-AnalyticalSystems. The CCU may receive data during sample preparation executionand may update a data repository and one or more displays. Data receivedduring sample preparation may include, but is not limited to: containerlocation, sample status, reagent use, wash buffer data, waste containerdata, etc. Other data received by a CCU from a PAS may include bar codedata which may indicate an item loaded into the AS.

According to one or more embodiments, a CCU may receive or provide oneor more inputs via a user interface or communicatively coupled devices.For example, a user interface of the CCU may include, but is not limitedto, login of one or more users, reporting, viewing of instrument(s)status, viewing of a work list, viewing of test results, anduser/operator management.

According to some embodiments, CCU communication with an AS may includebi-directional communication for a range of activities including, butnot limited to: startup, setup, processing, on-going communication, anddata updates. For example, startup data may include registration of aninstrument (e.g., an AS), receipt of data (e.g., item container data,reagent container data, sample container data, well information, etc.).The CCU may also receive a test schedule from one or more AnalyticalSystems. The CCU may receive data during sample preparation executionand may update a data repository and one or more displays. Data receivedduring sample preparation may include, but is not limited to: containerlocation, sample status, reagent use, wash buffer data, waste containerdata, etc. Other data received by a CCU from an AS may include bar codedata which may indicate an item loaded into the AS.

According to some embodiments, CCU 102 may also be connected to LIS 108via network connection 114. Network connection 114 may use a variety ofprotocols including, but not limited to, a health level 7 (HL7) basedinterface, or an American Society for Testing and Materials (ASTM) basedinterface. CCU 102 may receive one or more work orders and other datafrom LIS 108 via network connection 114. CCU 102 may also provide datasuch as test results to LIS 108. As described in greater detail below.CCU 102 may analyze test results prior to providing test results via LIS108, via a report or a display.

According to some embodiments, CCU 102 may communicate with othersystems. For example, a CCU may determine that one or more consumablematerials used for testing such as, for example, pipette tips, reagents,wash buffer, sample plates, and ETUs are getting low. CCU 102 mayinterface with an inventory or supply chain management system forordering or restocking supplies. Such an interface may be to an internalsystem or may provide order information to a vendor based system.

In addition to reports and a user interface of CCU 102, CCU 102 mayprovide notification to users via email, a SMS (Short Message Service)communication, a text message, a phone call, a page, or by otherelectronic communications. Notifications may be configured by anauthorized user to reach the user via a specified electronic address forone or more events. For example, an operator of CCU 102 may provide aphone number associated with wireless communication device 110 toreceive alerts associated with the processing of one or more sets ofsamples. An alert may occur if a consumable level is running low andneeds restocking, if a waste container is reaching capacity, if an errorcode has been received from PAS 104, AS 106, or CCU 102, or if a processhas completed. An operator monitoring CCU 102 may also receive anotification if an order has been received from LIS 108. The events thatprompt notifications, notification contact information (e.g., a phonenumber, an email address), and notification contact methods (e.g., phonecall, email, fax, page, SMS message, text message) may be configurable.

According to some embodiments CCU 102 may provide remote diagnosticinformation to one or more systems. Remote diagnostic information mayinclude error codes and other data received from a PAS, an AS, oranother instrument. Remote diagnostic information may also includecalibration information for one or more instruments, results, andstatistics associated with results. For example, carryover may beassessed by measuring the RLU (Relative Light Unit)/CO (Cutoff) ofnegative specimens that were processed just before and just after a highpositive specimen. Other statistics may be analyzed such as, forexample, a number of invalid test results for a population size and anumber of positive samples for a population size. This information maybe provided automatically by the CCU 102 or may be released by anoperator of CCU 102 to a remote system. Other remote diagnosticinformation may be associated with error codes. Certain error codes andassociated data may be provided to an external system by CCU 102. Forexample, if CCU 102 receives an error code indicating that a pipettinginstrument of PAS 104 has encountered an error, CCU 102 may provide dataassociated with the error to an external system. The external system maybe a support system of a vendor. Data associated with the error mayinclude data indicating a current state of PAS 104 (e.g., a status ofsamples currently being processed including samples processed by apipetter, the last calibration results of a pipetter, the serial number,bar code, manufacturer and other information associated with a pipetter,and a software version used by PAS 104). CCU 102 may produce one or morediagnostic or error reports to provide to an external support system.

According to one or more embodiments, a CCU may provide remote access toa diagnostic or support system. A CCU may implement audit tracking andother security measures to verify integrity of data and operations.Remote access may be provided via a virtual private network or usingother secure measures. Remote access may require an operator of a CCU oranother authorized user to provide access. A CCU may also export one ormore portions of data and provide them securely to a remote diagnosticand support team.

Remote diagnostic data provided by a CCU may provide an indication of acurrent or future service need. Remote diagnostic data may allow thescheduling of preventive maintenance based on received data. Analysis ofdiagnostic data provided from a plurality of CCUs may identify trends(e.g., maintenance periods) for one or more systems or instruments.

According to some embodiments, CCU 102 may receive information from anexternal system. Information may include diagnostic test information,troubleshooting information, software updates, and patches. Informationreceived from an external system may be used by an operator of CCU 102to troubleshoot one or more errors.

Of course, the CCU, or various parts of it, may be integrated into thePAS 104 itself, in which case the PAS 100 may be provided with a humaninterface to receive operating instructions and/or display systemstatus. Such an interface may include various interface elements knownin the art, such as a monitor, touch-screen monitor, keyboard, mouse,microphone, speaker, barcode reader, and so on. Similarly, one or moreportions of the CCU may be integrated into AS 106, in which case AS 106may provide access to CCU functionality via a human interface. While theshown arrangement of inputs and outputs has been selected for thisembodiment, it will be understood that other arrangements may be used inother embodiments.

FIG. 2 shows a module for control of and coordination between automatedsample processing systems, according to an embodiment. As illustrated,sample processing control and coordination module 210 may contain one ormore components including pre-analytical monitoring module 212,analytical monitoring module 214, worklist management module 216,reporting module 218, interface module 220, and error handling module222.

The description below describes network elements, computers, and/orcomponents of a system and method for portable device data archivingthat may include one or more modules. As used herein, the term “module”may be understood to refer to computing software, firmware, hardware,and/or various combinations thereof. Modules, however, are not to beinterpreted as software which is not implemented on hardware, firmware,or recorded on a processor readable recordable storage medium (i.e.,modules are not software per se). It is noted that the modules areexemplary. The modules may be combined, integrated, separated, and/orduplicated to support various applications. Also, a function describedherein as being performed at a particular module may be performed at oneor more other modules and/or by one or more other devices instead of orin addition to the function performed at the particular module. Further,the modules may be implemented across multiple devices and/or othercomponents local or remote to one another. Additionally, the modules maybe moved from one device and added to another device, and/or may beincluded in both devices.

Pre-analytical monitoring module 212 may monitor one or morepre-analytical systems such as, for example, PAS 104. Pre-analyticalmonitoring module 212 may track sample processing by one or morepre-analytical systems. Pre-analytical monitoring module 212 may alsotrack consumables such as, for example, pipette tips, reagents, washbuffer, sample plates, and ETUs. Tracked information may includeinformation used to calculate an amount of one or more consumablesrequired for scheduled sample processing (e.g., based on samples loadedfor processing at a PAS.) Other tracked consumable information mayinclude expiration information associated with consumable material, ashelf life of consumable material, and an opening date/time of containerof consumable material (e.g., a reagent pack). Other information trackedby pre-analytical monitoring module 212 may include a remaining capacityof one or more waste containers. Pre-analytical monitoring module 212may obtain data from a PAS which may be used to provide one or moreinterfaces, reports, and notifications on a CCU. Pre-analyticalmonitoring module 212 may also obtain diagnostic data, instrument data,and other status data. PAS data may be queried by pre-analyticalmonitoring module 212 or provided to pre-analytical monitoring module212. According to some embodiments, pre-analytical monitoring module 212may reside on a PAS and may transmit data to a CCU.

Analytical monitoring module 214 may monitor one or more analyticalsystems such as, for example, AS 106. Analytical monitoring module 214may track sample processing by one or more analytical systems.Analytical monitoring module 214 may also track consumables such as, forexample, trays, pipette tips, reagents, wash buffer, sample plates, andETUs. Tracked information may include information used to calculate anamount of one or more consumables required for scheduled sampleprocessing (e.g., based on samples loaded for processing at an AS.)Other tracked consumable information may include expiration informationassociated with consumable material, a shelf life of consumablematerial, and an opening date/time of container of consumable material(e.g., a reagent pack). Information tracked by analytical monitoringmodule 214 may include, but is not limited to, a remaining capacity ofone or more waste containers. Analytical monitoring module 214 mayobtain data from an AS which may be used to provide one or moreinterfaces, reports, and notifications on a CCU. Analytical monitoringmodule 214 may also obtain diagnostic data, instrument data, and otherstatus data. AS data may be queried by analytical monitoring module 214or provided to analytical monitoring module 214. According to someembodiments, analytical monitoring module 214 may reside on an AS andmay transmit data to a CCU.

Worklist management module 216 may track samples and provide dataindicating a status of samples on a pre-analytical system, a status ofsamples on an analytical system, a indication of results, a mapping ofsamples on a sample plate, and other sample management data. Worklistmanagement module 216 may provide the tracking of a sample from receiptof a work order, pre-analytical processing, analytical processing,results analysis, and release of results.

Reporting module 218 may provide one or more user interfaces andreports. Reports may include, but are not limited to: an individualpatient report; a results report; a plate map report; an assay report; areagent report; a controls report; and a sample location report.

Interface module 220 may provide interfaces to one or more externalsystems. External systems may include, but are not limited to, an LIS,an online inventory system, and a supply chain management system.

According to one or more embodiments, a CCU may provide remote access toa diagnostic or support system. A CCU may implement audit tracking andother security measures to verify integrity of data and operations.Remote access may be provided via a virtual private network or usingother secure measures. Remote access may require an operator of a CCU oranother authorized user to provide access. A CCU may also export one ormore portions of data and provide them securely to a remote diagnosticand support team.

Remote diagnostic data provided by a CCU may provide an indication of acurrent or future service need. Remote diagnostic data may allow thescheduling of preventive maintenance based on received data. Analysis ofdiagnostic data provided from a plurality of CCUs may identify trends(e.g., maintenance periods) for one or more systems or instruments.

Error handling module 222 may handle one or more errors received from apre-analytical system, an analytical system, a CCU, or another connectedinstrument or system. Error handling module 222 may handle one or moreerrors encountered with an interface to an external system. According tosome embodiments, error handling module 222 may provide notifications oferrors via reporting module 218. Error handling module 222 may alsoprovide notification to users via email, a SMS (Short Message Service)communication, a text message, a phone call, a page, or by otherelectronic communications. Notifications may be configured by anauthorized user to reach the user via a specified electronic address forone or more events.

FIG. 3 depicts a method for control of and coordination betweenautomated sample processing systems, according to an embodiment. Atblock 302, the method 300 for control of and coordination betweenautomated sample processing systems may receive one or more orders forsample processing at a central control unit. For example, orders may bereceived at a CCU from a LIS or another external system. An operator mayalso enter orders. According to some embodiments, order information mayinclude a requested test id, test name, or test protocol for one or moresamples. Additional order information may include a sample id andpatient information (e.g., a patient id, name, date of birth, address).Other order information may be received. According to some embodiments,a CCU receiving an order may automatically assign a test protocol to oneor more samples associated with an order. In some embodiments, anoperator at a CCU may assign a test protocol to one or more samplesassociated with an order.

At block 304, the method 300 may transmit one or more portions of anorder to a pre-analytical system for processing. Transmitted informationmay include one or more sample ids, test protocol information, and otherdata that may be used by the analytical system for processing andtracking of samples.

The CCU may receive information about consumable materials used by thepre-analytical system for sample processing. For example, bar codes,RFID tags, or other identifiers may be placed on consumable materialssuch as reagent packs, pipette tips, wash buffer containers, sampleplates. Analytical systems, pre-analytical systems, and otherinstruments may scan consumable materials as they are loaded into thesystems. This data may be provided to a CCU. Analytical systems,pre-analytical systems, and other instruments may track consumption ofconsumable materials and communicate this data to the CCU. At block 306,the CCU may determine whether there are sufficient materials on apre-analytical system for processing the samples in the order. Accordingto one embodiment, a CCU may contain data regarding the materialspresent on a system and the system (e.g., a pre-analytical system) maycontain logic determining whether such materials are sufficient forprocessing. If a PAS contains sufficient materials for sample processingthe method 300 may continue at block 312. If a PAS does not containsufficient materials for sample processing, the method 300 may continueat block 308.

At block 308, one or more operators may be notified. According to someembodiments, an operator may be notified remotely (e.g., paged, sent anemail, sent a text message, or sent a voicemail). A user interfaceassociated with the CCU, an interface of the PAS, or interfaces of bothsystems may provide notifications (e.g., pop-up alerts on a screen)about required materials. According to some embodiments, apre-analytical system may not begin processing a sample until sufficientmaterials are loaded for processing of the sample.

At block 310, an operator may resolve the issue by loading one or moreconsumable materials for the sample processing (e.g., loading a reagentpack). A user interface at the CCU may provide instructions on loadingan appropriate consumable material which may include diagrams and clickthrough steps. The pre-analytical system may detect the loading of theconsumable material (e.g., by scanning a barcode on a package) and mayprovide the information to the CCU. Processing of one or more samplesmay begin. In some embodiments, an instrument such as a PAS may beginprocessing a first set of samples as soon as it receives them andloading of additional consumable materials for the remaining loadedsamples may not interrupt the processing.

At block 312, the CCU may monitor processing. The CCU may receive datafrom a plurality of components of pre-analytical systems and analyticalsystems. The CCU may receive data associated with: automated pipettingsubsystems or components of a PAS; incubators; supply containers (e.g.,levels which may be monitored by sensors); luminometers, fluorometers;incubators; agitators, orbital shakers, actuators (e.g., an access armor gripper used to transport samples), capping and decapping units, andother instruments. The CCU may contain or receive one or more indicatorsof errors. For example, a CCU may receive an indicator of an error froma PAS (e.g., a pipettor drops a tip). A CCU may also process data to seeif it meets specified criteria. Specified criteria may, by way ofnon-limiting example, include a range. For example, a CCU may detect anerror if an incubator is outside of a specified range. The specifiedcriteria may vary depending on a test protocol of a sample currentlybeing processed by an instrument (e.g., the acceptable temperature rangefor an incubator may vary by test protocol or the desired agitationperiod may vary by protocol). If an error is detected the method 300 maycontinue at block 316. If no errors are detected, the method maycontinue at block 318.

At block 316 the identified error may be resolved. Resolution may differdepending on the cause of the error. Resolution may result in one ormore samples being marked as invalid (e.g., insufficient sample size).Resolution may involve continuing a process after a problem has beencorrected.

At block 318, completion of one or more samples at the PAS may bedetected. At block 320, an operator may be notified. As illustrated inFIG. 1, an operator may manually transfer one or more sample plates orother containers from a pre-analytical system to an analytical system.The analytical system may begin processing one or more samples. Prior toprocessing or during processing the CCU may determine whether theanalytical system has sufficient materials for processing. According toone embodiment, a CCU may contain data regarding the materials presenton a system and the system (e.g., an analytical system) may containlogic determining whether such materials are sufficient for processing.The CCU and/or analytical system may provide one or more notificationsregarding materials (e.g., reagents, wash buffers) depending on levels.

At block 322, the CCU may monitor processing. The CCU may receive datafrom the analytical system associated with one or more instruments. TheCCU may receive an error notification or may identify an error fromreceived data. The CCU may use one or more specified criteria toevaluate portions of the data received from the analytical system. Forexample, a CCU may determine whether an sample cell count is adequatebased on a measurement of turbidity against one or more specifiedcriteria. If an error is detected the method 300 may continue at block326. If no error is detected, the method 300 may continue at block 328.

At block 326, the identified error may be resolved. Resolution maydiffer depending on the cause of the error. Resolution may result in oneor more samples being marked as invalid (e.g., low cellularity).Resolution may involve continuing a process after a problem has beencorrected.

At block 328 results may be received and analyzed. The CCU may perform aplurality of tests to verify the results.

At block 330, the results may be released. Release of the results may bethrough one or more reports and/or transmission of one or more portionsof the results to a LIS. Additionally, release of results may enable anoperator to schedule one or more samples for reflex testing.

Referring now to FIG. 4, there is depicted a system for acceptance ofand control of manually created samples and automated analysis of suchsamples. The manual pre-analytical chemistry (MPAC) process of the CCUmay allow manual sample preparation of specimens to be entered andtracked (e.g., PreservCyt or SurePath specimens). The MPAC interface ofthe CCU may also allow a user to create plate maps in order for manuallyprepared samples to be transferred to plates for analysis by an AS. TheMPAC interface may allow a user to add samples from manually preparedplates to a CCU WorkList. As such, the MPAC components of the CCU mayperform one or more the following: identifying sample tubes, extractiontubes, plates, and reagent kits used during MPAC; communicating sampletube, extraction tube, plate, plate map, and reagent kit information tothe CCU; tracking sample location from sample tube to extraction tube toplate well; creating plate maps and transmitting plate maps to the CCUso that they may be processed by an AS.

The MPAC interface of the CCU may accept barcode entries, manuallyentered text, and other inputs. For example, a barcode readercommunicatively coupled to the CPU may allow entry of plate barcodes,sample barcodes, extraction tube identifiers, reagent kit barcodes, andother identifiers. Data manually entered via a keyboard may requireconfirmation (e.g., two entry fields may be provided to require a userto confirm a number. The MPAC interface of the CCU may allow a user toassign a test order to a sample barcode. The MPAC interface may alsoallow a user to update test progress associated with a sample (e.g.,associate a sample with an extraction tube, add/remove samples to andfrom a worklist, and associate a well on a plate with a sample). TheMPAC interface may provide several different views allowing a user tonavigate information including views organized by sample, plate,worklist, supplies, etc.

The MPAC interface may enforce one or more rules. For example, a usermay be required to have controls or calibrators on a plate beforecommitting a plate map. The MPAC interface may enforce other rules(e.g., allowing a sample to occupy only one well per plate for HPVassays, ensuring that users cannot place samples into wells reserved forcalibrators on the plate map, ensuring that users cannot place samplesinto unavailable wells on the plate map, allow samples associated with atest or tests to be placed only on a plate map associated with the sametest or tests. According to some embodiments, the MPAC software mayidentify to the user, via a graphical UI, the next location where asample should be placed.

An exemplary diagram of inputs and outputs of a CCU is depicted in FIG.5. As illustrated in FIG. 5, a CCU may receive one or more assaydefinitions. An assay protocol may have an external object definition.Assay objects may be loosely coupled with a core CCU system. An assayversioning scheme may be provided by a CCU to associate results with theversion of an assay used to create results. The CCU Assay Definitionsinput source may allow loading assay protocol definitions from an XMLfile in a way that allows new assay definitions to be deployed withoutsoftware or database changes.

The CCU Database, AS, PAS, and LIS may be external systems to a CCU thatmay serve both as a source of input and as a target of output. The CCUarchitecture may be designed in a manner to hide specific hardware andsoftware interface details of the AS and PAS. An instrument interfacelibrary component may be used for instrument communication so anyinstrument that can communicate through the instrument interface librarycan be integrated into a CCU system in the future.

The CCU system may provide integration with a variety of LaboratoryInformation Systems (LIS's) which may be installed at a customer'sfacility. Two exemplary LIS communication protocols that may besupported are ASTM 1381/1394 and HL7. ASTM 1394 and HL7 are data formatstandards, while ASTM 1381 is a low-level transport protocol standardthat is used by ASTM 1394. The communication transport used for the HL7protocol may be TCP/IP. While the protocols, transports, and command setfor communicating between instruments and an LB may be standardizedflexibility may be built into an LB interface in a CCU to accommodateeither LIS vendor-specific data and behaviors, or customer site-specificrequirements.

The interface between CCU and LIS may be a bidirectional interface. TheLIS-to-CCU direction may provide lab orders and patient data that needsto be translated into test runs on the instruments and the CCU-to-LISdirection may provide the communication of test results back to LIS andquerying LIS for patient information for a sample being processed by theCCU.

Referring now to FIGS. 6-8, there is depicted an exemplary graphicalview of the logical composition of the major components of a CCU system,based on exemplary high level components and common services. FIG. 6illustrates components of a CCU operator interface. A CCU operatorinterface may be a primary user interface that a work cell operator usesto view and manage data and workflow state within a CCU database. TheCCU operator interface module may implements the primary operator userinterface for a CCU system. Functionality implemented by a CCU Operatorinterface module may include, but are not limited to:

-   -   authentication of operators as they login to the CCU Operator        Interface;    -   allowing operators with sufficient privileges to manage other        operator accounts;    -   allowing operators to view the active work lists for each        instrument in the work cell, where a work list entry may        consists of a test protocol identifier, a sample identifier,        current status of the test, and any events or comments        associated with the work list entry;    -   allowing operators to view a reflex list of samples that have        tested positive and may need to have a follow-up test run;    -   allowing operators to view status summary information for one or        more instruments in the work cell, with status summary        information consisting of test in progress, reagent and/or other        supply status, connectivity of instrument;    -   allowing operators to run and print reports on completed and        in-progress work on the instruments, including patient report,        results report, plate map report, assay report, reagent report,        controls report; and    -   allowing operators to manage error and event information from        the CCU and from each instrument in the work cell.

The CCU operator interface module of FIG. 6 may include other modulessuch as for example, a CCU Common Business Module 604, an assay module606, a reporting module 608, a workflows module 610, a components module612, and an entities module 614.

Presentation module 660 may contain UI components and UI ProcessComponents. UI components may include screen controls and logic thatcontrol the behavior of the control itself. UI Process Components mayinclude larger groupings of screen controls and process flow and eventpassing between controls to manage a higher-level processing task.

According to some embodiments, the physical implementation of the CCUOperator interface and the physical implementation of these logicalarchitectural components may follow a variation on theModel-View-Presenter (MVP) design pattern. The pattern followed may beModel-View-ViewModel (MVVM) and is a pattern that is based onModel-View-Presenter, but is tailored to take advantage of features inWindows Presentation Framework. Windows Presentation Framework (WPF) maybe used for UI development framework for developer user interfaces in.Net and may be the user interface framework used to implement the CCUOperator Interface.

The MVVM pattern may take advantage of WPF's binding infrastructure.Properties of the View Model may be bound to graphical components of theView in a loosely coupled way and reduce or eliminate the traditionalevent handling and control updating logic that is involved with otherframeworks. The data binding system in WPF may also support automaticdata input validation, further reducing coding requirements in the Viewlayer and providing for standardized input validation error reporting.

Application façade 616 may be a mapping layer that converts data betweenthe UI layer and the data storage layer, based on a typical differencesin how data is structured for presentation versus how data is stored ina database or other repository.

A CCU Common Business Module 604 may be a business logic layer that mayencapsulate data and behavior into objects usable by the UI andServices. For a CCU, examplary candidate objects in this layer may besample, Test Run, Patient, etc. A CCU Common Business Module 604 mayimplement a class library interface for one or more major businessobjects of the system. According to some embodiments, some modules maybe separate (e.g., assay and reporting). Functionality implemented bythis module may include, but is not limited to:

-   -   Encapsulation of behavior and data access/data storage for all        major objects in the system, including: Instruments, Instrument        physical attributes (e.g., racks, trays, containers), Work        lists, Samples, Patients, Test results, Sample containers (e.g.,        plates, tubes, ETUs, wells), Assay reagents, Events, and        Operators;    -   Providing workflow operations across one or more business object        components listed above;    -   Providing helper classes for communicating between a User        Interface (UI) and a business module; and    -   Providing domain objects for communicating with the data        services layer for data storage.

The Assay Module 606 may incorporate assay loading from external files,assay version management, and data analysis of samples against assays.The Assay Module 606 may be a data reduction module that may implement aclass library interface for assay and results calculation (datareduction). Exemplary functionality implemented by this module mayinclude, but is not limited to:

-   -   Encapsulation of behavior and data access/data storage for one        or more assay and test results calculation objects in a system,        including: Assay, Assay configuration, Assay protocol,        Calibration, Calibration parameters, Control, Control        parameters, RLU limit parameters, and Data reduction parameters;    -   Providing workflow operations across one or more business object        components;    -   Providing helper classes for communicating between the UI and        this business module;    -   Providing domain objects for communicating with the data        services layer for data storage;    -   Dynamic loading of assay protocol definitions from XML files;        and    -   Management of assay versioning and corresponding results        versioning.

Reporting Module 608 may implement functionality for the definition ofreports, the generation of reports from live data, and the printing andexporting of report data.

Reporting Module 608 may implement a class library interface forreporting services used by the user interface modules. Functionalityimplemented by this module may include, but is not limited to:

-   -   Providing a utility to define reports that may be executed by        name and with parameters by higher level classes. Exemplary        reports include: an Individual Patient Report; a Results Report;        a Plate Map Report; an Assay Report; a Reagent Report; and a        Controls Report;    -   Providing a user interface for accessing a list of available        reports, specifying parameters for the reports, and managing the        report result storage (e.g., on-screen, Excel, and PDF);    -   Providing classes to convert object-relational data (object        graphs) to data sets for report generation; and    -   Providing utility classes to support internationalization (e.g.,        strings, datetime, currency, printed page form factors).

CCU Data Module 620 may include object-data persistence for a CCU CommonBusiness Module, data archival services, data purging, and backup andrestoration functionality. CCU Data Module 620 may implement datapersistence for domain objects from CCU Common Business Module 604,Assay Module 606, and Report Module 608 components. In addition, it mayprovide other database and file utilities and services. Functionality ofthis module may include:

-   -   Providing object persistence service that performs        object-relational data mapping and save/restore of objects        to/from a relational database;    -   Providing utility interfaces for data archiving and purging for        use in GUI or console applications;    -   Providing utility interfaces for data backup and restore for use        in GUI or console applications; and    -   Providing utility classes for data serialization and mapping for        class libraries and service programs.

Referring to FIG. 7, Instrument Communication Service 706 may include acommand and response interface used by instruments to communicate withthe CCU Common Business Services. According to some embodiments,Instrument Communication Service 706 may implement a Windows Servicehost interface and client library that may provide a communicationinterface used by instruments to communicate status to the CCU and tolook up information from the CCU. This module may include a clientlibrary that may provide an interface that instruments bind to,providing flexibility for the actual service to be located on the localor a remote machine. Functionality provided by this module may include,but is not limited to:

-   -   Providing a class interface that may allow instruments to        interact with the CCU Common Business module. The types of        operations that instruments may perform with the class library        may include: Instrument registration; Operator login; Sample        container management; Reagent container management; and Event        management.    -   Providing a Windows Service that may respond to requests from        the instrument interface client library. The Windows Service        services requests through use of the CCU Common Business module        and Assay (Data Reduction) module.

LIS Interface Service 708 may implement a Windows Service and clientlibrary that may provide a bi-directional interface to customer LISsystems. This service may support both ASTM 1384/1391 and HL7communication protocols for LIS communication as well as otherprotocols. Functionality provided by this module may include:

-   -   Supporting patient data streaming;    -   Supporting automatic run/sample results transmission;    -   Supporting manual run/sample results transmission;    -   Supporting querying active database for patient data for given        samples;    -   Supporting querying LIS host for patient data for given samples;    -   Supporting associating patient data to samples in the database,        upon patient streaming or querying (LIS or database);    -   Supporting periodic patient data purge;    -   Supporting notification to the CCU Operator Interface of run        packet transmission completion; and    -   Supporting notification to the CCU Operator Interface of LIS        transmission connection status changes.

System Monitoring Service 710 may monitor the availability of keyprograms and services of the CCU system and alerting of operators if akey process or service is unavailable. System Monitoring Service 710 mayimplement a Windows Service host interface and corresponding monitoringagent programs that may monitor the “health” of program and servicemodules of the CCU system. Functionality provided by this module mayinclude:

-   -   Providing a host interface that receives system monitoring        events and routes events received to the CCU Common Business        Module and Common Utility Concerns for logging and notification;    -   Providing monitoring agents that monitor specific services and        program modules (File Watcher, Instrument Communication Service,        CCU Database) and send events to the System Monitoring host        service; and    -   Providing configurability of what monitored events trigger        notification.

Monitored activities include, but are not limited to: (Process is alive;Process responding to heartbeat request; Events logged to event log thatexceed configured warning thresholds; Database full; and Log file(s)full).

According to some embodiments, a CCU Remote Operator Interface may beprovided. A CCU remote operator interface may provide access to one ormore portions of functionality remotely and may be designed for a mobileclient (e.g., an IPAD, a cell phone, a PDA, a laptop, etc.). A CCUremote operator interface may be accessible via a LAN (e.g., wirelessaccess) to provide mobility within a worksite or remotely (e.g., via asecure VPN) to allow access to travelers.

Referring now to FIG. 8, XML Parsing 812 may translate between XML filesand the Instrument Communication Services. This service process may runcontinuously on an AS machine to monitor and act on asynchronous filecreation between a CCU and AS. XML Parsing 812 may implement a WindowsService that may read and write XML files that may be used tocommunicate directly with an AS instrument. (XML file-basedcommunication may be a method of interacting with the AS instrument'scontrol software.) Once an XML file is parsed and the request isunderstood, this service may use the Instrument Communication Servicesclient library to interact with the CCU. Responsibilities of this modulemay include:

-   -   Translating XML file-based command requests coming from the AS        instrument into appropriate calls to the Instrument        Communication Service module to send status and lookup requests        from the AS to the CCU;    -   Creating XML files from responses received from the CCU to send        results back to the AS;    -   Monitoring specified folders for new XML files generated from an        AS machine and processing each file as it is found; and    -   Providing a recovery/retry service for files that fail to        processed successfully.

As illustrated by the Cross-cutting module 650 of FIGS. 6-8, thefollowing may be common services used by one or more other modules.Cross-cutting module 650 may be a class library of common utilityconcerns (also called “cross-cutting services”) that may be used in oneor more programs and services modules of the system. The specific majorlevels of functionality provided by this library may include: Security;Logging and Error Handling; Transaction Support; Communication; Inputand Data Validation; and Localization.

Security may relate to protecting data and controlling access to thesystem. Encryption, user authentication, and checksum may be elementsincluded in a Security module.

Logging and Error Handling may include a common method of logging errorsand events, alerting operators of critical errors, and performing auditlogging of operation and data access by operators. This module may beconfigurable in terms of what level of information is logged, whatalerting methods are used, and what error log repositories are used.

A Transaction Support module may provide a common means of markingtransaction boundaries and of committing or rolling back transactionsbased on business logic and error detection in the business logic. Thismodule may also be extended to cover object invalidation, which mayoccur if a transaction is rolled back.

A Communication module may provide general client/server conversationalcommunication services (e.g., as supported by WCF or by lower-levelinterfaces like Sockets).

An Input and Data Validation module may provide common validationservices for use by a user interface and/or parsing layers. Commonvalidations may consolidate code that may typically spread throughoutthe application and may often written redundantly and inconsistently.

A Localization module may provide services for returning an appropriatestring, date, currency, sort order based on the locale of the operator.

FIG. 9 is a diagram illustrating module dependencies and interactions,according to an embodiment. FIG. 10 depicts a diagram of a physical viewof the CCU software in terms of the major software subcomponents of CCU,according to some embodiments. FIG. 11 shows a more detailed view of theMVVM design pattern implemented in the CCU Operator Interface, accordingto some embodiments.

FIG. 12 is a sequence diagram illustrating communication between anInstrument Client Library and an Instrument Service, according to anembodiment. The Instrument Client Library may communicate to theInstrument Service through .Net Remoting. Net Remoting may be a serviceprovided by the .Net framework that may allow objects to communicationacross process boundaries and across the network. The interfaces to use.Net Remoting may be straightforward and, once a class is declared as“remoting enabled’, the target and consumer source code look nodifferent than if using local objects.

As illustrated in FIG. 12, the Instrument Client Library may makes anexplicit call to Activate a remote top-level service object. This“extra” code to obtain a reference to a service object may not beexposed to the end-consumer of the Instrument Client Library, such thatthe consumer of the library may not care or know that it iscommunicating with a remote service. Top-level service objects in theInstrument Service may be declared as “Server Activated Objects” (SAOs),meaning they may live on a server and a proxy object may be created onthe client machine. They may be Singleton objects, as well, meaning theyare created the first time when requested by a client, but stay inexistence indefinitely after created (until the service exits).Spring.Net, through its integration with .Net Remoting, may instantiateone or more top-level service objects, as shown in the sequence diagramin the “startup” phase. The Instrument Library Client interface may bevery high-level and its interface may deal with large-grained operationslike “get reagent container” and “save reagent container”. According tosome embodiments, there may be no direct database access from the clientlibrary or the application using the client library. One or moredatabase access operations may be performed by the Instrument LibraryService. When a high-level call is made to the Instrument Library theentire object graph may be made available to the caller, also, via .NetRemoting. The objects referenced by the high level object returned canbe returned as a proxy or by value, depending upon how the classdeclaration is set up. Containers, wrappers, and repositories may bedeclared as proxy objects by inheriting from MarshalByRefObject, whilenon-container objects are declared using the Serializable attribute inthe class definition and are returned by-value in the object graph. Thelibrary interaction may be designed around the paradigm of “retrieve alot of related data, work on it, save it all back when finished workingon it”.

FIG. 13 is a diagram relating logical components of an AS, a CCU, and aPAS, to the physical component names, according to an embodiment.

FIG. 14 depicts an exemplary organizational chart of interface screens.

FIG. 15 depicts a user interface for viewing a sample worklist,according to an embodiment. As illustrated in FIG. 15, a worklist mayprovide sample details including, but not limited to: a result, a sampleID, a patient ID, a sample date and time, and an assay protocol. Aworklist may be sortable, filterable, and scrollable.

FIG. 16 depicts a user interface for viewing a sample location report,according to an embodiment. A sample location report may includelocation details for a sample such as, for example, a rack id, aposition id, a sample id, a patient id, and sample date and time, and anassay protocol. A sample location report may be sortable, filterable,and scrollable.

FIG. 17 depicts a user interface for viewing preparation and testingtimelines for Analytical and Pre-Analytical systems, according to anembodiment. Timelines may include a start time for one or more jobs(e.g., pre-analytical processing and analytical processing), a currenttime, a projected end time, an instrument operator, a number of samplesbeing processed, and other timeline details.

FIG. 18 depicts a user interface for remote monitoring of apre-analytical system, according to an embodiment. Pre-analytical systemmonitoring details may include, for example, a current status ofmaterials in one or more reagent bays (e.g., beads, buffer, controls,oil, etc.), a current status of disposable items (e.g., ETU tips,transfer tips, ETUs, etc.), a current status of one or more wastecontainers, a current status of a reject holding area, a current inputstatus (e.g., plates queued for input), and a current status of anoutput area (e.g., plates ready for output to an AS).

FIG. 19 depicts a user interface for releasing samples from a worklistfor genotyping, according to an embodiment. An interface for releasingsamples from a worklist may provide a count of samples to be releasedand individual sample details.

FIG. 20 depicts a user interface for reflex sample informationverification, according to an embodiment. Sample information may includea result, a rack id, a position id, and a sample id. A user control maybe provided to trigger reflex testing of one or more samples.

FIG. 21 depicts a user interface for selecting a view of reflexinformation according to an embodiment.

FIG. 22 depicts a user interface for a plate map highlighting samplesselected for reflex testing, according to an embodiment.

FIG. 23 depicts a user interface for sample reflex listing, according toan embodiment.

FIG. 24 depicts a user interface for sample location reporting forreflex samples, according to an embodiment.

FIG. 25 depicts a user interface for selecting reports, according to anembodiment.

FIG. 26 depicts a user interface for alerts associated with attachedinstruments, according to an embodiment. As depicted, a user interfacemay contain a dashboard or other area displaying icons or otherindicators of instruments associated with a CCU. An alert may beassociated with an icon of an instrument and may be selectable for auser to obtain more information.

FIG. 27 depicts a user interface displaying an alert detail, accordingto an embodiment. As depicted an alert detail may provide instrumentstatus details (e.g., an AS or a PAS running low on a reagent, adisposable item, or other supplies). Alerts may also signal completionof a process, an error, or other conditions.

FIG. 28 depicts a user interface for viewing instrument statusinformation, according to an embodiment. An instrument statusinformation interface may allow a CCU operator to remotely diagnose acondition triggering an alert.

FIG. 29 depicts a user interface for providing operator help, accordingto an embodiment. Operator help may be associated with an alert and mayprovide instructions allowing an operator to resolve a conditiontriggering an alert.

FIG. 30 depicts a method for analyzing a plate that was processed on anAnalytical System, according to an embodiment. The method may begin atblock 3002. When plate measurement is initiated, software may beprovided with a plate background value from a luminometer at thebeginning plate measurement. The following background correctionalgorithm may be applied to one or more measured wells on a plate priorto initiating any of the data reduction. This may apply to calibrators,controls, and patient specimens on a plate. The initial RLU valuemeasured for a well may be referenced as Well RLURaw. For each measuredwell on the plate, the reported RLU value for the well may be calculatedas follows:Well RLUcorrected=Well RLURaw−Plate Background

If the Well RLUCorrected value is determined to be less than zero, thenthe Well RLUcorrected value may be set to zero.

At block 3004, calibration mode of an AS may be determined. If thecalibration mode is time interval, the method may continue at block3006. If the calibration mode is per plate, the method may continue atblock 3010.

At block 3006, it may be determined whether calibrators are on a plate.If calibrators are on a plate, the method may continue at block 3010. Ifcalibrators are not on a plate, the method may continue at block 3008.

At block 3008, it may be determined whether there is a valid calibrationthat can be used. If there is a valid calibration that can be used, themethod may continue at block 3016. If there is not a valid calibrationthat can be used the assay may be indicated as invalid at block 3020.

At block 3010 calibrators may be evaluated. Evaluation of a calibratoris discussed in further detail in reference to FIG. 31 below.

At block 3012 it may be determined whether the calibrators are valid. Ifthe calibrators are valid the method may continue at block 3014. If thecalibrators are not valid the method may continue at block 3020.

At block 3014, assay cutoff values may be calculated. Assay controls maybe evaluated at block 3016.

At block 3018 it may be determined whether controls for at least onesample type are valid. If controls for at least one sample type arevalid, the method may continue at block 3022. If controls are not validfor at least one sample type the method may continue at block 3020.

At block 3020, an assay may be determined to be invalid and the methodmay end at block 3032.

At block 3022, non-blank wells on a plate may be evaluated. At block3024, the content of a non-blank well may be determined. If a non-blankwell contains a control, the method may continue at block 3026. If anon-blank well contains a patient specimen, the method may continue atblock 3028.

At block 3026 a control may be evaluated. Evaluation of a control isdiscussed in further detail in reference to FIG. 32 below.

At block 3028, a patient specimen may be evaluated.

At block 3030, it may be determined whether any more un-blank wellsremain for evaluation on a plate. If further un-blank wells are to beevaluated, the method may return to block 3022. If no further un-blankwells are to be evaluated, the method may end at block 3032.

FIG. 31 depicts a method for analyzing a calibrator replicate accordingto an embodiment. According to some embodiments, calibrators may beevaluated on a per-shift or a per-plate basis, depending on modespecified for the assay. In per shift calibration mode, each platereferences one set of valid calibrators for the entire shift. At block3102, calibrator evaluation may be initiated.

At block 3104, it may be determined if more than one calibratorreplicate has a processing error. If more than one calibrator replicatehas a processing error, the calibrator replicate may be marked asinvalid at block 3108. If one or no calibrator replicates haveprocessing errors, the method may continue at block 3016.

At block 3106 the Relative Light Unit (RLU) of a calibrator replicatemay be compared against specified minimum and maximum values. If the RLUvalue of the calibrator replicate falls within specified values, themethod may continue at block 3110. If the RLU value of the calibratorreplicate falls outside of specified values, the calibrator replicatemay be marked as invalid at block 3108.

At block 3110 it may be determined whether all calibrator replicateshave been evaluated. If all calibrator replicates have been evaluated,the method may continue at block 3112. If more calibrator replicatesremain for evaluation the method may return to block 3104.

At block 3112 it may be determined whether more than one calibratorreplicate has been indicated as invalid. If more than one calibratorreplicate has been indicated as invalid, the calibration may bedetermined to be invalid at block 3126. If one or no calibratorreplicates have been indicated as invalid the method may continue atblock 3114.

At block 3114, the mean, the standard deviation, and the percentage of acoefficient of variation may be calculated for a calibrator replicate.At block 3116, the percentage of the coefficient of variation for acalibrator replicate may be compared against a specified maximum value.If the percentage of the coefficient of variation for a calibratorreplicate is less than or equal to a specified maximum threshold, thecalibration may be indicated as valid at block 3118. If the percentageof the coefficient of variation for a calibrator replicate exceeds aspecified threshold, the method may continue at block 3120.

At block 3120 it may be determined whether one calibrator replicate hasalready been invalidated. If a calibrator replicate has already beeninvalidated the calibration may be determined to be invalid at block3126. If no calibrator replicate has already been invalidated, themethod may continue to block 3122.

At block 3122, a dixon outlier algorithm may be performed. According tosome embodiments, the Dixon Outlier Algorithm may only be applied ifthere are at least three calibrator replicates to analyze. The softwaremay sort the non-validated replicates from lowest to highest RLU. Thesoftware may calculate R_(high) and R_(low), as follows:R _(high)=(X _(n) −X(_(n-1)))/(X _(n) −X ₁)R _(low)=(X ₂ −X ₁)/(X _(n) −X ₁)where X₁, X₂, etc. . . . is a replicate RLU (sorted from low=1 tohigh=n), and n is the number of replicates. The scenario where X_(n)=X₁would always lead to a division by zero error. However, because thecalibrator replicates are sorted low to high, if X_(n)=X1 thecalibrators may pass the % CV check and the Dixon Outlier Algorithm maynot be applied.

The software may determine X_(n) as an outlier, if R_(high)>r10(n),where r10(n), is determined from the table below for an alpha of 0.01.

The software may determine X₁ as an outlier, if R_(low)>r10(n), wherer10(n), is determined from the table below for an alpha of 0.01.

According to some embodiments, only one calibrator replicate may berejected.

Number of Calibrator Replicates (n) r10(n) Alpha = 0.01 3 r10(3) 0.988 4r10(4) 0.889 5 r10(5) 0.780 6 r10(6) 0.698

At block 3124 if an outlier replicate has not been identified, thecalibration may be determined to be invalid at block 3126. If an outlierreplicate has been identified the identified outlier calibratorreplicate may be indicated as invalid at block 3128.

At block 3130, the mean, the standard deviation, and the percentage of acoefficient of variation may be calculated for the remaining calibratorreplicates. At block 3132, the percentage of the coefficient ofvariation for a calibrator replicate may be compared against specifiedmaximum value. If the percentage of the coefficient of variation for acalibrator replicate is less than or equal to a specified maximumthreshold, the calibration may be indicated as valid at block 3118. Ifthe percentage of the coefficient of variation for a calibratorreplicate exceeds a specified threshold, the calibration may bedetermined to be invalid at block 3126.

FIG. 32 depicts a method for assay control evaluation according to anembodiment. At block 3202 control evaluation may be initiated.

At block 3204 it may be determined whether a control is invalid due to aprocessing error. If a control is invalid due to a processing error, thecontrol may be indicated as invalid at block 3208. If a control is notinvalid due to a processing error the method may continue at block 3206.

At block 3206 the Relative Light Unit (RLU) of a control may be comparedagainst specified minimum and maximum values. If the RLU value of thecontrol falls within specified values the method may continue at block3210. If the RLU value of the control falls outside of specified values,the control may be indicated as invalid at block 3208.

At block 3210, a control ratio may be calculated for a control. Thecontrol ratio may be calculated as follows:Control Ratio=Well RLU_(corrected)/Assay cutoff**assay cutoff may be specific to a specimen type.

If the control ratio falls within specified values the control mayindicated as valid at block 3212. If the control ratio falls outside ofspecified values, the control may be indicated as invalid at block 3208.

While the invention has been described by way of examples and preferredembodiments, it is understood that the words which have been used hereinare words of description, rather than words of limitation. Changes maybe made, within the purview of the appended claims, without departingfrom the scope and spirit of the invention in its broader aspects.Although the invention has been described herein with reference toparticular means, materials, and embodiments, it is understood that theinvention is not limited to the particulars disclosed. The inventionextends to all equivalent structures, means, and uses which are withinthe scope of the appended claims.

What is claimed is:
 1. A system for managing a plurality of instrumentsfor processing a plurality of biological samples, the system comprising:at least one pre-analytical instrument; at least one analyticalinstrument; at least one user interface device configured to displayinformation in worklists, error notifications, and operatinginstructions; and one or more computing devices communicatively coupledto the pre-analytical instrument, the analytical instrument, and theuser interface device, wherein the one or more computing devices areconfigured to: receive an order to process a plurality of biologicalsamples; create a worklist, wherein the worklist includes a sampleidentifier and an assay protocol for each of the biological samples tobe processed by the pre-analytical instrument and the analyticalinstrument; instruct the user interface device to display information inthe worklist; monitor the pre-analytical instrument and the analyticalinstrument during processing of the biological samples, wherein themonitoring includes: identifying one or more biological samples that arenot, being processed by the pre-analytical instrument or the analyticalinstrument in accordance with the assay protocols associated with thosebiological samples in the worklist; instructing the user interfacedevice to display a first error notification, wherein the first errornotification provides the sample identifiers associated with theidentified biological samples in the worklist; and interruptingprocessing of at least one of the identified biological samples that arenot being processed by the pre-analytical instrument or the analyticalinstrument in accordance with the assay protocols associated with thosebiological samples in the worklist; receive consumable materialinformation from the pre-analytical instrument or the analyticalinstrument, wherein the consumable material information includes anamount of one or more consumable materials remaining; instruct the userinterface device to display a second error notification when the amountof one or more consumable materials remaining falls below a firstpredetermined threshold, wherein the second error notification deliversa link to a set of operating instructions describing how to loadadditional consumable materials into the pre-analytical instrument orthe analytical instrument; and interrupt processing of at least one ofthe biological samples when the amount of one or more consumablematerials remaining, falls below a second predetermined threshold,wherein the second predetermined threshold is below the firstpredetermined threshold.
 2. The system of claim 1, wherein the one ormore computing devices are further configured to: receive waste materialinformation from the pre-analytical instrument or the analyticalinstrument, wherein the waste material information includes an amount ofone or more waste materials generated; instruct the user interfacedevice to display a third error notification when the amount of one ormore waste materials generated exceeds a third predetermined threshold;and interrupt processing of at least one of the biological samples whenthe amount of one or more waste materials generated exceeds a fourthpredetermined threshold, wherein the fourth predetermined threshold isabove the third predetermined threshold.
 3. The system of claim 1:wherein the worklist further includes a sample location for each of thebiological samples to be processed by the pre-analytical instrument andthe analytical instrument, and wherein the first error notificationfurther provides the sample locations of the biological samples that arenot being processed by the pre-analytical instrument or the analyticalinstrument in accordance with the assay protocols associated with thosebiological samples in the worklist.
 4. The system of claim 3, whereinthe first error notification identifies one or more portions of theassay protocols with which the pre-analytical instrument or theanalytical instrument failed to comply.
 5. The system of claim 1 furthercomprising: an incubator, wherein at least one of the assay protocolsrequires biological sample processing in a specified temperature rangeand the one or more computing devices control the incubator to processthe biological samples according to the assay protocol.
 6. The system ofclaim 1, wherein at least one of the assay protocols specifies anagitation period for at least some of the biological samples and the oneor more computing devices control an agitator to agitate at least someof the biological samples according to the assay protocol.
 7. The systemof claim 1, wherein at least one of the assay protocols requires apredetermined minimum number of calibrators to be placed on one or moreplates.
 8. The system of claim 7, wherein at least one of the assayprotocols requires one or more of the calibrators to be within apredetermined Relative Light Unit (RLU) range.
 9. The system of claim 1:wherein the worklist further includes one or more of a patientidentifier, a sample location, or a sample result for each of thebiological samples to be processed by the pre-analytical instrument andthe analytical instrument, and wherein the user interface device isfurther configured to: display, in response to a request from a user,one or more of sample identifiers, patient identifiers, assay protocols,sample locations, or sample results associated with one or more of thebiological samples; and display, in response to a request from the user,one or more of consumable material information, waste materialinformation, or one or more testing timelines for the pre-analyticalinstrument or the pre-analytical instrument.
 10. The system of claim 1:wherein the one or more computing devices are configured to select atleast one of the processed biological samples for reflex testing, andwherein the user interface device is further configured to display aplate map illustrating locations of one or more of the selectedbiological samples, wherein the plate map highlights one or more of theselected biological samples.
 11. A method for managing a plurality ofinstruments for processing a plurality of biological samples, the methodcomprising: receiving an order to process a plurality of biologicalsamples; creating a worklist, wherein the worklist includes a sampleidentifier and a sample status for each of the biological samples to beprocessed by a pre-analytical instrument and an analytical instrument;receiving status data for at least some of the biological samples fromthe pre-analytical instrument or the analytical instrument; updating thesample statuses for the at least some of the biological samples in theworklist based on the received status data; instructing a user interfacedevice to display one or more of the updated sample statuses along withthe sample identifiers associated with those biological samples in theworklist; instructing the user interface device to display testingtimelines for the pre-analytical and analytical instruments, wherein thetesting timelines include a projected end time; receiving consumablematerial information from the pre-analytical instrument or theanalytical instrument, wherein the consumable material informationincludes an amount of one or more consumable materials remaining; andwhen the amount of one or more consumable materials remaining fallsbelow a first predetermined threshold: instructing the user interfacedevice to display a first error notification; instructing the userinterface device to display a set of operating instructions describinghow to load additional consumable materials into the pre-analyticalinstrument or the analytical instrument; and restocking thepre-analytical instrument or the analytical instrument with additionalconsumable materials before the amount of one or more consumablematerials remaining falls below a second predetermined threshold,wherein the second predetermined threshold is below the firstpredetermined threshold, and wherein processing of at least one of thebiological samples is interrupted when the amount of one or moreconsumable materials remaining is allowed to fall below the secondpredetermined threshold.
 12. The method of claim 11 further comprising:receiving waste material information from the pre-analytical instrumentor the analytical instrument, wherein the waste material informationincludes an amount of one or more waste materials generated; and whenthe amount of one or more waste materials generated exceeds a thirdpredetermined threshold: instructing the user interface device todisplay a second error notification; instructing the user interfacedevice to display a set of operating instructions describing how toremove waste materials from the pre-analytical instrument or theanalytical instrument; and removing at least some of the waste materialsfrom, the pre-analytical instrument or the analytical instrument beforethe amount of one or more waste materials generated exceeds a fourthpredetermined threshold, wherein the fourth predetermined threshold isabove the third predetermined threshold, and wherein processing of atleast one of the biological samples is interrupted when the amount ofone or more waste materials generated is allowed to exceed the fourthpredetermined threshold.
 13. The method of claim 12, wherein the one ormore consumable materials and the one or more waste materials includeone or more types of pipette tips, one or more types of reagents, one ormore types of wash buffers, one or more types of sample plates, and oneor more types of extraction tube units (ETUs).
 14. The method of claim11, wherein the timeline further includes a start time and a currenttime.
 15. A method for managing a plurality of instruments forprocessing a plurality of biological samples, the method comprising:receiving an order to process a plurality of biological samples;creating a worklist, wherein the worklist includes a sample identifierand an assay protocol for each of the biological samples to be processedby a pre-analytical instrument and an analytical instrument; instructinga user interface device to display information in the worklist;monitoring the pre-analytical instrument and the analytical instrumentduring processing of the biological samples, wherein the monitoringincludes determining whether at least some of the biological samples arebeing processed by the pre-analytical instrument and the analyticalinstrument in accordance with the assay protocols associated with thosebiological samples in the worklist; when at least one of thepre-analytical instrument or the analytical instrument fails to processat least one of the biological samples in accordance with the assayprotocol associated with that biological sample in the worklist:instructing the user interface device to display a first errornotification, wherein the first error notification provides the sampleidentifiers of the biological samples that are not being processed bythe pre-analytical instrument or the analytical instrument in accordancewith the assay protocols associated with those biological samples in theworklist; and interrupting processing of the biological samples that arenot being processed by the pre-analytical instrument or the analyticalinstrument in accordance with the assay protocols associated with thosebiological samples in the worklist; when at least some of the biologicalsamples were processed by the pre-analytical instrument and theanalytical instrument in accordance with the assay protocols associatedwith those biological samples in the worklist: selecting at least one ofthe processed biological samples for reflex testing; instructing theuser interface device to display a plate map illustrating locations ofone or more of the selected biological samples, wherein the plate maphighlights one or more of the selected biological samples; andtriggering reflex testing of one or more of the selected biologicalsamples.
 16. The method of claim 15 further comprising: receivingconsumable material information from the pre-analytical instrument orthe analytical instrument, wherein the consumable material informationincludes an amount of one or more consumable materials remaining; whenthe amount of one or more consumable materials remaining falls below afirst predetermined threshold, instructing the user interface device todisplay a second error notification, wherein the second errornotification delivers a link to a set of operating instructionsdescribing how to load additional consumable materials into thepre-analytical instrument or the analytical instrument; and when theamount of one or more consumable materials remaining falls below asecond predetermined threshold, interrupting processing of at least oneof the biological samples, wherein the second predetermined threshold isbelow the first predetermined threshold.
 17. The method of claim 16further comprising: receiving waste material information from, thepre-analytical instrument or the analytical instrument, wherein thewaste material information includes an amount of one or more wastematerials generated; when the amount of one or more waste materialsgenerated exceeds a third predetermined threshold, instructing the userinterface device to display a third error notification; and when theamount of one or more waste materials generated exceeds a fourthpredetermined threshold, interrupting processing of at least one of thebiological samples, wherein the fourth predetermined threshold is abovethe third predetermined threshold.
 18. The method of claim 17, whereinthe one or more consumable materials and the one or more waste materialsinclude one or more types of pipette tips, one or more types ofreagents, one or more types of wash buffers, one or more types of sampleplates, and one or more types of extraction tube units (ETUs).
 19. Themethod of claim 15: wherein the worklist further includes a samplelocation for each of the biological samples to be processed by thepre-analytical instrument and the analytical instrument, and wherein thefirst error notification further provides the sample locations of thebiological samples that are not being processed by the pre-analyticalinstrument or the analytical instrument in accordance with the assayprotocols associated with those biological samples in the worklist. 20.The method of claim 19, wherein the first error notification identifiesone or more portions of the assay protocols with which thepre-analytical instrument or the analytical instrument failed to comply.21. The method of claim 15, wherein at least one of the assay protocolsrequires an incubator to operate in a specified temperature range. 22.The method of claim 15, wherein at least one of the assay protocolsspecifies an agitation period for at least some of the biologicalsamples.